Home About us Contact
|
Home About us Contact | ||
|
|
||
Racemization
Kinds of Racemization Selected AbstractsAsymmetric Synthesis of (S)-Mirtazapine: Unexpected Racemization through an Aromatic ipso -Attack MechanismEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2008Marco van der Linden Abstract An asymmetric synthesis of (S)-mirtazapine has been achieved from the synthesis of the racemate by using (S)-1-methyl-3-phenylpiperazine as the starting material. Unfortunately, significant racemization was encountered in the final step, which involved an electrophilic aromatic ring closure of a alcohol by concentrated sulfuric acid. A significantly higher ee was observed when polyphosphoric acid (PPA) was used instead. A remarkable correlation between the amount of PPA used and the ee of the product was revealed, namely, an increase in the ee upon decreasing the amount of PPA. This trend was paralleled by the formation of an increasing amount of a side-product upon lowering the amount of PPA. The racemization and formation of a side-product can be explained by an ipso -attack mechanism during the electrophilic aromatic ring-closure reaction. This mechanism was supported by a mechanistic study using a deuterium-labeled substrate.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Biocatalytic Racemization of (Hetero)Aryl-aliphatic ,-Hydroxycarboxylic Acids by Lactobacillus spp.EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2006Proceeds via an Oxidation, Reduction Sequence Abstract The biocatalytic racemization of a range of (hetero)aryl- and (di)aryl-aliphatic ,-hydroxycarboxylic acids has been achieved by using whole resting cells of Lactobacillus spp. The essentially mild (physiological) reaction conditions ensure the suppression of undesired side reactions, such as elimination, decomposition or condensation. Cofactor/inhibitor studies using a cell-free extract of Lactobacillus paracasei DSM 20207 reveal that the addition of redox cofactors (NAD+/NADH) leads to a distinct increase in the racemization rate, while strong inhibition is observed in the presence of Thio-NAD+, which suggests that the racemization proceeds by an oxidation,reduction sequence rather than involvement of a "racemase" enzyme. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Distribution of piperitone oxide stereoisomers in Mentha and Micromeria species and their chemical synthesesFLAVOUR AND FRAGRANCE JOURNAL, Issue 4 2007Olga Larkov Abstract Chiral GC,MS analyses of natural and synthetic trans- and cis- piperitone oxide were performed on an Rt- ,DEX-sm capillary column in order to clarify the stereochemistry of their enantiomeric forms. Only enantiomerically pure laevo-rotatory piperitone oxides, (1S,2S,4S)- trans- piperitone oxide and (1S,2S,4R)- cis- piperitone oxide, were detected by chiral analyses of Micromeria fruticosa (L.) Druce and Mentha longifolia L. The occurrence of the cis - and trans -piperitone oxides was dependent on the population of the species. In all cases (1S,2S,4S)- trans- piperitone oxide was detected together with (4S)-piperitone, while (1S,2S,4R)- cis- piperitone oxide was detected together with (4R)-piperitone in the plants analysed. The four stereoisomers of trans - and cis -piperitone oxide were obtained by alkaline epoxidation of both (4R)- and (4S)-piperitone. The formation of the 1,2-epoxide can take place on either side of the 1,4-substituted six-membered ring. Racemization at C4 was observed under alkaline epoxidation reaction conditions due to keto-enol tautomerism. Copyright © 2007 John Wiley & Sons, Ltd. [source] Type I Collagen Racemization and Isomerization and the Risk of Fracture in Postmenopausal Women: The OFELY Prospective StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2002Patrick Garnero Ph.D. Abstract The Asp1211 residue of the1209AHDGGR1214 sequence of the C-terminal cross-linking telopeptide of type I collagen (CTX) can undergo spontaneous post-translational modifications, namely, racemization and isomerization, which result in the formation of four isomers: the native form (,- L) and three age-related forms, that is, an isomerized form (,- L), a racemized form (,- D), and an isomerized/racemized (,- D) form. Previous studies have suggested that changes in the pattern of type I collagen racemization/isomerization, which can be assessed in vivo by measuring the degradation products of the CTX isoforms, may be associated with alterations of bone structure. The aim of this study was to examine prospectively the value of the different urinary CTX isoforms and their related ratio in the prediction of osteoporotic fractures in 408 healthy untreated postmenopausal women aged 50-89 years (mean, 64 years) who were part of the OFELY cohort. During a median 6.8 years follow-up, 16 incident vertebral fractures and 55 peripheral fractures were recorded in 65 women. The baseline levels of the four CTX isoforms in women who subsequently had a fracture were compared with those of the 343 women who did not fracture. At baseline, women with fractures had increased levels of ratios of native ,- L -CTX to age-related isoforms (,- L, ,- D, and ,- D) compared with controls (p < 0.01). In logistic regression analysis after adjustment for age, prevalent fractures, and physical activity, women with levels of ,- L/,- L, ,- L/,- D, and ,- L/,- D -CTX ratios in the highest quartile had a 1.5- to 2-fold increased risk of fractures compared with women with levels in the three lowest quartiles with relative risk (RR) and 95% CI of 2.0 (1.2-3.5), 1.8 (1.02-2.7), and 1.5 (0.9-2.7), respectively. Adjustment of ,- L/,- L and ,- L/,- D -CTX ratios by the level of bone turnover assessed by serum bone alkaline phosphatase (ALP)- or femoral neck bone mineral density (BMD) decreased slightly the RR, which remained significant for the ,- L/,- L -CTX ratio (RR [95%] CI, 1.8 [1.1-3.2] after adjustment for bone ALP, 1.8 [1.03-3.1] after adjustment for BMD, and 1.7 [0.95-2.9] after adjustment for both bone ALP and BMD). Women with both high ,- L/,- L -CTX ratio and high bone ALP had a 50% higher risk of fracture than women with either one of these two risk factors. Similarly, women with both increased CTX ratio and low femoral neck BMD (T score < ,2.5) had a higher risk of fracture with an RR (95% CI) of 4.5 (2.0-10.1). In conclusion, increased urinary ratio between native and age-related forms of CTX, reflecting decreased degree of type I collagen racemization/isomerization, is associated with increased fracture risk independently of BMD and partly of bone turnover rate. This suggests that alterations of type I collagen isomerization/racemization that can be detected by changes in urinary CTX ratios may be associated with increased skeletal fragility. [source] Photoinduced Racemization of an Optically Active Helical Polymer Formed by the Asymmetric Polymerization of 2,7-Bis(4- tert -butylphenyl)fluoren-9-yl Acrylate,ANGEWANDTE CHEMIE, Issue 49 2009Takeshi Sakamoto Dr. Ein Lichttrick: Ein durch asymmetrische anionische Polymerisation hergestelltes optisch aktives helicales Polymer mit Vorzugshändigkeit ging bei Photobestrahlung eine Stereomutation ein. Dagegen blieb die Helix beim Erhitzen stabil (siehe Bild). Diese photoinduzierte Racemisierung eines synthetischen helicalen Polymers verlief ohne Änderung der chemischen Bindung wie Bindungsbildung, Bindungsspaltung oder Isomerisierung einer Doppelbindung. [source] ChemInform Abstract: An Efficient Method for Racemization of (S)-3-Carbamoylmethyl-5-methylhexanoic Acid.CHEMINFORM, Issue 38 2009Ting Wu Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Thiyl Radical Mediated Racemization of Benzylic Amines.CHEMINFORM, Issue 47 2006Stephanie Escoubet Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Unexpected Racemization in the Series of 4,5-Disubstituted [2.2]Paracyclophanes.CHEMINFORM, Issue 35 2006R. P. Zhuravsky Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Biocatalytic Racemization of ,-Hydroxycarboxylic Acids at Physiological Conditions.CHEMINFORM, Issue 34 2005Silvia M. Glueck Abstract For Abstract see ChemInform Abstract in Full Text. [source] One-Pot Synthesis of Helical Aromatics: Stereoselectivity, Stability Against Racemization, and Assignment of Absolute Configuration Assisted by Experimental and Theoretical Circular Dichroism.CHEMINFORM, Issue 12 2005Masashi Watanabe Abstract For Abstract see ChemInform Abstract in Full Text. [source] Optically Active Telluronium Imides: Optical Resolution, Absolute Configuration, and Mechanism of Racemization.CHEMINFORM, Issue 49 2003Toshio Shimizu No abstract is available for this article. [source] ChemInform Abstract: A Novel and Facile Racemization of Chiral 1,1,-Biaryl-2,2,-dicarboxylic Acids.CHEMINFORM, Issue 40 2001Masanori Hatsuda Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Racemization and Rearrangement of 1,2-Dihydro-1,3,5-triazines: A Novel Reversible Thermal Electrocyclic Reaction.CHEMINFORM, Issue 31 2001Gordon Lowe Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Asymmetric Total Synthesis of Fredericamycin A: An Intramolecular Cycloaddition PathwayCHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2005Shuji Akai Dr. Abstract The asymmetric total synthesis of the potent antitumor antibiotic fredericamycin A ((S)- 1) was achieved by the intramolecular [4+2] cycloaddition of the silylene-protected styrene derivative (S)- 7 followed by the aromatic Pummerer-type reaction of the sulfoxide (S)- 5. Although we had already succeeded in the total synthesis of racemic 1 by the same approach, synthesis of its asymmetric version was more complicated than we had expected due to the difficulties involved in constructing the quaternary carbon center and the tendency of this center to undergo facile racemization. Racemization of this center during the installation of the acetylene moiety on the dione (R)- 8 was the most serious aspect. Systematic studies of its DE-ring analogue (R)- 25 revealed that racemization of the quaternary carbon center proceeded by a retro-aldol,aldol reaction of the initial adduct, (1R)- 39,a -Li, and that the degree of racemization was dependent on the reaction temperature. The racemization process could be completely depressed by keeping the reaction temperature at ,78,°C. The construction of the stereogenic quaternary carbon center was achieved by the lipase-catalyzed desymmetrization of the prochiral 1,3-diol 9,a bearing the DEF-ring moiety. These studies enabled us to attain the asymmetric total synthesis of (S)- 1 while completely retaining the chiral integrity created by the enzymatic reactions. [source] Gaseous Ion Activation Dynamics: The Role of the Bulk Gas in the Racemization of Chiral Oxonium IonsCHEMPHYSCHEM, Issue 10 2004Antonello Filippi Dr. Abstract The kinetics of the inversion of configuration of a family of chiral oxonium ions, that is, O-protonated 1-aryl-1-methoxyethanes [YMe+], were investigated in two different gaseous media (in CH3X with X=F and X=Cl) at 720 torr of pressure and in the temperature range: 25,140,°C. The activation parameters of the [YMe+] inversion reaction were found to obey two different isokinetic relationships (IKR), depending on the nature and the position of the substituents in the oxonium ions and on the nature of the bulk gas employed. The observation of two IKR for the same family of reactions was related to a switchover in the resonant vibrational energy exchange between the reactants' critical mode, active in the transition state (,), and the discrete vibrational levels , of the bulk gas. In CH3F, this vibrational,vibrational coupling switchover concerns the out-of-plane CF,,,HO bending (the , family) and the H3CF stretching (the , family) modes in the proton-bound [CH3F,YMe+] complex. In CH3Cl, the coupling switchover concerns the out-of-plane CCl,,,HO bending (the , family) and the H3CCl methyl group rocking (the , family) modes in the proton-bound [CH3Cl,YMe+] complex. The [YMe+] activation dynamics also determine the inversion dynamics. The [YMe+]ret,[YMe+]invisomerization for the , family involves the same "thermodynamically most favorable" transition state in both the CH3F and the CH3Cl media, whereas the same process for the , family proceeds through different, dynamically favored transition states. [source] Racemization of the gastrointestinal antisecretory chiral drug esomeprazole magnesium via the pyramidal inversion mechanism: A theoretical studyCHIRALITY, Issue 9 2010Hili Marom Abstract The pyramidal inversion mechanisms of the 6-methoxy and the 5-methoxy tautomers of (S)-omeprazole were studied, employing ab initio and DFT methods. The conformational space of the model molecule (S)-2-[(3-methyl-2-pyridinyl)methyl]sulfinyl-1H -benzimidazole was calculated, with respect to rotations around single bonds, at the B3LYP/6-311G(d,p) level. All of the resulting conformations were used as starting points for full optimizations of (S)-omeprazole, at B3LYP/6-31G(d), B3LYP/6-311G(d,p), B3LYP/6-311++G(d,p), B3LYP/6-311G(2df,2pd), MP2/6-31G(d), and MP2/6-311G(d,p) levels. Four distinct pathways were found for enantiomerization via the pyramidal inversion mechanism for each of the tautomers of (S)-omeprazole. Each transition state, in which the sulfur, the oxygen and the two carbon atoms connected directly to the sulfur are in one plane, connects two diastereomeric minima. The enantiomerization is completed by free rotation around the sulfur,methylene bond, and around the methylene,pyridine ring bond. The effective Gibbs' free energy barrier for racemization ,G of the two tautomers of (S)-omeprazole are 39.8 kcal/mol (5-methoxy tautomer) and 40.0 kcal/mol (6-methoxy tautomer), indicating that the enantiomers of omeprazole are stable at room temperature (in the gas phase). The 5-methoxy tautomer of (S)-omeprazole was found to be slightly more stable than the 6-methoxy tautomer, in the gas phase. The energy barrier (,G,) for the(S,M) (S,P) diastereomerization of (S)-omeprazole due to the rotation around the pyridine chiral axis was very low, 5.8 kcal/mole at B3LYP/6-311G(d,p). Chirality 2010. © 2010 Wiley-Liss, Inc. [source] Asymmetric Synthesis of (S)-Mirtazapine: Unexpected Racemization through an Aromatic ipso -Attack MechanismEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2008Marco van der Linden Abstract An asymmetric synthesis of (S)-mirtazapine has been achieved from the synthesis of the racemate by using (S)-1-methyl-3-phenylpiperazine as the starting material. Unfortunately, significant racemization was encountered in the final step, which involved an electrophilic aromatic ring closure of a alcohol by concentrated sulfuric acid. A significantly higher ee was observed when polyphosphoric acid (PPA) was used instead. A remarkable correlation between the amount of PPA used and the ee of the product was revealed, namely, an increase in the ee upon decreasing the amount of PPA. This trend was paralleled by the formation of an increasing amount of a side-product upon lowering the amount of PPA. The racemization and formation of a side-product can be explained by an ipso -attack mechanism during the electrophilic aromatic ring-closure reaction. This mechanism was supported by a mechanistic study using a deuterium-labeled substrate.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Biocatalytic Racemization of (Hetero)Aryl-aliphatic ,-Hydroxycarboxylic Acids by Lactobacillus spp.EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2006Proceeds via an Oxidation, Reduction Sequence Abstract The biocatalytic racemization of a range of (hetero)aryl- and (di)aryl-aliphatic ,-hydroxycarboxylic acids has been achieved by using whole resting cells of Lactobacillus spp. The essentially mild (physiological) reaction conditions ensure the suppression of undesired side reactions, such as elimination, decomposition or condensation. Cofactor/inhibitor studies using a cell-free extract of Lactobacillus paracasei DSM 20207 reveal that the addition of redox cofactors (NAD+/NADH) leads to a distinct increase in the racemization rate, while strong inhibition is observed in the presence of Thio-NAD+, which suggests that the racemization proceeds by an oxidation,reduction sequence rather than involvement of a "racemase" enzyme. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Asymmetric Synthesis of ,-Fluorinated ,-Amino Acid DerivativesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2005Deepak M. Shendage Abstract Asymmetric alkylation of (S)-Boc-BMI (1a, BMI = 2- tert -butyl-3-methylimidazolidin-4-one) and its ,-methyl derivative 1b with 2-fluoroallyl tosylate, subsequent mild acidic deprotection of the products 2a and 2b, and basic hydrolysis of the thus formed N -methylamides 4a and 4b gave (S)-2-amino-4-fluoropent-4-enoic acid (5a) and (S)-2-amino-4-fluoro-2-methylpent-4-enoic acid (5b). Basic hydrolysis of compound 4a was accompanied by partial racemization, which was overcome by applying a new stereoconservative deamidation procedure. The alkylated cis -configured product 2a formed under kinetic control epimerized on refluxing with 2 n NaOH to give the thermodynamically more stable trans isomer 9. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] A dating intercomparison study on Late Stone Age coastal midden deposits, South AfricaGEOARCHAEOLOGY: AN INTERNATIONAL JOURNAL, Issue 6 2008Mark D. Bateman The southern and western coastlines of South Africa have an extensive archaeological record with many sites associated with widespread eolian deposits. While much of this rich archaeological record is based on cave sites, evidence of Late Stone Age occupation is additionally preserved in the form of open-site shell middens. We present here a comparative study of the application of amino acid racemization (AAR), optically stimulated luminescence (OSL), and radiocarbon analyses to three Late Stone Age (LSA) midden sites found within dunes on the southern coastline of South Africa. Preliminary geochronological analyses suggest that middens offer opportunity to fill in gaps in what is still a fragmentary archaeological record. Results show OSL and radiocarbon ages in good agreement, illustrating the potential to date not only the middens but also the surrounding dunes that constituted the dwelling sites. AAR results show increasing ratios with age and also that the application of paired shell and "whole rock" AAR can provide insights into the degree of biogenic sediment recycling at buried midden sites. However, the work also highlights that caution is required when OSL sampling sediment associated with middens which may have undergone human disturbance and that further work is required to improve the regional marine reservoir correction for radiocarbon dating in this part of South Africa. The study also illustrates that AAR will only provide useful data provided that middens have been sufficiently deeply buried to overcome fluctuations in environmental variables that affect the racemization rate and that inter-genus comparisons should be avoided. © 2008 Wiley Periodicals, Inc. [source] Stratigraphic and Morphologic Constraints on the Weichselian Glacial History of Northern Prins Karls Forland, Western SvalbardGEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 4 2000Torbjörn Andersson Uncertainty remains if ice,free marginal areas existed on the west coast of Svalbard during the Late Weichselian. Field mapping and correlation to well dated raised beach sequences on nearby Brøggerhalvøya reveal the existence of two generations of raised beach deposits on northern Prins Karls Forland. Distinct beach ridges rise up to the inferred Late Weichselian marine limit at 18 m a.s.l. Discontinuous pre,Late Weichselian beach deposits rise from the Late Weichselian marine limit up to approximately 60 m a.s.l. Expansion of local glaciers during the Late Weichselian is indicated by the limited distribution of a till that overlies parts of the older beach sequence. Stratigraphic data and chronological control indicate deposition in a shallow marine environment before 50 ka bp. Correlation to stratigraphic sites on western Svalbard suggests deposition at c. 70 ±10 ka. Glaciotectonic structures disclose expansion of local glaciers into the For,landsundet basin during stage 4 or late stage 5 high relative sea level. Palaeotemperature estimates derived from amino acid ratios indicate that during the time interval c. 70 to 10 ka the area was exposed to cold subaerial temperatures with low rates of racemization. Pedogenesis and frost,shattered clasts at the contact between c. 70 ka deposits and Holocene deposits further indicate a prolonged period of subaerial polar desert conditions during this time interval. The evidence suggests that the Barents Sea ice sheet did not extend across northern Prins Karls Forland during the Weichselian. It is inferred that during the Late Weichselian, ice was drained throughout the major fjords on the west coast of Svalbard and that relatively large marginal areas experienced polar desert conditions and minor expansions of local glaciers. [source] Stabilizing effect of intramolecular lewis base toward racemization of optically active selenoxidesHETEROATOM CHEMISTRY, Issue 3 2007Takahiro Soma 2-(Methylchalcogenomethyl)diphenyl selenoxides 1 and 2-{2,-(N,N-dimethylamino)ethyl}phenyl alkyl (or aryl) selenoxides 2, which were expected to be stabilized toward racemization by intramolecular coordination, were synthesized and optically resolved into their enantiomers on an optically active column using high-performance liquid chromatography. Relationship between the absolute configurations and the chiroptical properties of the enantiomers was clarified by comparing with those of sulfur analogues. Stabilities toward racemization of optically active selenoxides 1a and 1b were nearly equal to that of 2-{(N,N-dimethylamino)methyl}diphenyl selenoxide and mesityl phenyl selenoxide. The rates of racemization for optically active selenoxides 2 were found to be faster than that of 2-{(N,N-dimethylamino)methyl}phenyl alkyl (or aryl) selenoxides. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:301,311, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20299 [source] The Addition Reaction of Samarium Enolates and 2-Haloenolates Derived from Esters, and Amides to Imines.ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 17 20094-Diamino Esters or Amides, Totally Stereoselective Synthesis of Enantiopure Abstract The addition reaction of samarium enolates and 2-haloenolates derived from esters and amides to imines takes place in an efficient manner. A novel protocol to perform the addition reaction of samarium enolates derived from esters or amides to chiral 2-aminoimines, with total stereoselectivity and without racemization, is also reported. The use of samarium enolates in place of other classic metallic enolates (lithium, magnesium, etc.) could be a valuable alternative to obtain enantiopure 3,4-diamino esters or amides, when enolates of low basicity are necessary. [source] Efficient, Enantioselective Organocatalytic Synthesis of Trichostatin AADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 10-11 2006Shilei Zhang Abstract An efficient, highly stereocontrolled total synthesis of trichostatin A (1) has been achieved in 9 steps with 17.4,% overall yield and >99,% optical purity from readily available achiral starting materials. The key features of this synthesis include the L -proline-promoted, highly enantioselective cross-aldol reaction as a crucial step for the construction of the C-6 chiral center and the minimization of racemization by final step oxidation of the OH group to a ketone at position 7. [source] Polymer-Supported Bisacetoxybromate(I) Anion ,-An Efficient Co-Oxidant in the TEMPO-Mediated Oxidation of Primary and Secondary AlcoholsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 5 2003Marco Brünjes Abstract A polymer-bound reagent for the efficient oxidation of primary alcohols to aldehydes and secondary alcohols to ketones in the presence of a catalytic amount of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) is described. The oxidation process is particular mild and allows one to prepare aldehydes with ,-chirality without racemization. This also includes the synthesis of ,-aminoaldehydes. In most cases, work-up of this heavy metal-free oxidation is achieved by simple filtration followed by removal of the solvent. Insight into the role of the bromate(I) anion in the oxidation process was gained from the TEMPO-mediated oxidation of benzaldehyde in the presence of the hypochlorite anion loaded on an anion exchange resin. [source] Type I Collagen Racemization and Isomerization and the Risk of Fracture in Postmenopausal Women: The OFELY Prospective StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2002Patrick Garnero Ph.D. Abstract The Asp1211 residue of the1209AHDGGR1214 sequence of the C-terminal cross-linking telopeptide of type I collagen (CTX) can undergo spontaneous post-translational modifications, namely, racemization and isomerization, which result in the formation of four isomers: the native form (,- L) and three age-related forms, that is, an isomerized form (,- L), a racemized form (,- D), and an isomerized/racemized (,- D) form. Previous studies have suggested that changes in the pattern of type I collagen racemization/isomerization, which can be assessed in vivo by measuring the degradation products of the CTX isoforms, may be associated with alterations of bone structure. The aim of this study was to examine prospectively the value of the different urinary CTX isoforms and their related ratio in the prediction of osteoporotic fractures in 408 healthy untreated postmenopausal women aged 50-89 years (mean, 64 years) who were part of the OFELY cohort. During a median 6.8 years follow-up, 16 incident vertebral fractures and 55 peripheral fractures were recorded in 65 women. The baseline levels of the four CTX isoforms in women who subsequently had a fracture were compared with those of the 343 women who did not fracture. At baseline, women with fractures had increased levels of ratios of native ,- L -CTX to age-related isoforms (,- L, ,- D, and ,- D) compared with controls (p < 0.01). In logistic regression analysis after adjustment for age, prevalent fractures, and physical activity, women with levels of ,- L/,- L, ,- L/,- D, and ,- L/,- D -CTX ratios in the highest quartile had a 1.5- to 2-fold increased risk of fractures compared with women with levels in the three lowest quartiles with relative risk (RR) and 95% CI of 2.0 (1.2-3.5), 1.8 (1.02-2.7), and 1.5 (0.9-2.7), respectively. Adjustment of ,- L/,- L and ,- L/,- D -CTX ratios by the level of bone turnover assessed by serum bone alkaline phosphatase (ALP)- or femoral neck bone mineral density (BMD) decreased slightly the RR, which remained significant for the ,- L/,- L -CTX ratio (RR [95%] CI, 1.8 [1.1-3.2] after adjustment for bone ALP, 1.8 [1.03-3.1] after adjustment for BMD, and 1.7 [0.95-2.9] after adjustment for both bone ALP and BMD). Women with both high ,- L/,- L -CTX ratio and high bone ALP had a 50% higher risk of fracture than women with either one of these two risk factors. Similarly, women with both increased CTX ratio and low femoral neck BMD (T score < ,2.5) had a higher risk of fracture with an RR (95% CI) of 4.5 (2.0-10.1). In conclusion, increased urinary ratio between native and age-related forms of CTX, reflecting decreased degree of type I collagen racemization/isomerization, is associated with increased fracture risk independently of BMD and partly of bone turnover rate. This suggests that alterations of type I collagen isomerization/racemization that can be detected by changes in urinary CTX ratios may be associated with increased skeletal fragility. [source] Synthesis and NMR spectroscopic studies of optically active derivatives of ,-aminobutenoic acids and 2-amino-pyrrolin-4-onesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2001Margarita Petroliagi An efficient method for the preparation of optically active derivatives of ,-amino-butenoic acids and their cyclic derivatives, 2-amino-pyrrolin-4-ones, from ,-amino acids is described. Partial racemization accompanies the formation of initial unsaturated ,-amino-,-hydroxy esters 5,8, as determined by chiral HPLC. [source] Synthesis and application of N -[1-(4-(4-fluorophenyl)-2,6-dioxocyclohexylidene)ethyl] (Fde)-protected amino acids for optimization of solid-phase peptide synthesis using gel-phase 19F NMR spectroscopyJOURNAL OF PEPTIDE SCIENCE, Issue 4 2009Maciej Pudelko Abstract N -[1-(4-(4-fluorophenyl)-2,6-dioxocyclohexylidene)ethyl] (Fde) protected amino acids have been prepared and applied in solid-phase peptide synthesis monitored by gel-phase 19F NMR spectroscopy. The Fde protective group could be cleaved with 2% hydrazine or 5% hydroxylamine solution in DMF as determined with gel-phase 19F NMR spectroscopy. The dipeptide Ac- L -Val- L -Val-NH2 12 was constructed using Fde- L -Val-OH and no noticeable racemization took place during the amino acid coupling with N,N,-diisopropylcarbodiimide and 1-hydroxy-7-azabenzotriazole or Fde deblocking. To extend the scope of Fde protection, the hydrophobic nonapeptide LLLLTVLTV from the signal sequence of mucin MUC1 was successfully prepared using Fde- L -Leu-OH at diagnostic positions. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Investigation of cis/trans ratios of peptide bonds in AVP analogues containing N -methylphenylalanine enantiomersJOURNAL OF PEPTIDE SCIENCE, Issue 1 2006Emilia Sikorska Abstract The solution conformation of vasopressin analogues, modified at positions 2 and 3 with N -methylphenylalanine or its enantiomer, [D -MePhe2,MePhe3]AVP and [MePhe2,D -MePhe3]AVP, were studied by 2D NMR spectroscopy in H2O/D2O and theoretical calculations (EDMC/ANALYZE). In the case of [MePhe2,D -MePhe3]AVP, the synthesis afforded two products, A and B, which had identical molecular ions and similar retention times on HPLC. This finding was explained by racemization of Cys1, which gave an additional analogue, [D -Cys1,MePhe2,D -MePhe3]AVP (B). The possibility is not excluded of racemization of Cys1 in the remaining analogues of this series. However, only in the case of [MePhe2,D -MePhe3]AVP was this process so distinct that two strong peaks in the HPLC chromatogram were observed. The NMR spectra of all the analogues showed several distinct sets of residual proton resonances. This suggests that the peptides adopt more than two groups of conformations in H2O/D2O. This fact is due to cis/trans isomerization. Two more populated isomers arise from the cis/trans isomerization across the 2,3 peptide bond in [D -MePhe2,MePhe3]AVP and [MePhe2,D -MePhe3]AVP (A) and across the 1,2 peptide bond in [D -Cys1,MePhe2,D -MePhe3]AVP (B). Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Polymer-bound alkyltriazenes for mild racemization-free esterification of amino acid and peptide derivativesJOURNAL OF PEPTIDE SCIENCE, Issue 10 2004Joachim Smerdka Abstract A novel tool for polymer-assisted solution phase (PASP) esterification of amino acid and peptide derivatives has been developed. When treated with carboxylic acids, polymer-bound alkyltriazenes react with a loss of nitrogen and transfer of the alkyl moiety to the carboxylate anion to form the corresponding alkyl esters. There are no limitations with regard to either the protecting groups or the nature of the amino acid. Furthermore no racemization occurs at the chiral centers of the amino acids as demonstrated by chiral GC-MS analyses. Alkyltriazene-resins were also applied successfully to the esterification of peptide acids and other peptidic structures, such as tripalmitoyl- S -glyceryl-cysteine (Pam3Cys). The triazene-mediated esterification reaction is exceptionally mild, and there is no need for prior activation of the carboxy groups. This method is therefore particularly suitable for the alkylation of complex peptidomimetic structures prone to racemization and for acid-sensitive structures. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||